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长链非编码RNA UCA1通过调控miR-185-5p/HOXA13轴介导喉鳞状细胞癌细胞的增殖和转移。

Long non-coding RNA UCA1 mediates proliferation and metastasis of laryngeal squamous cell carcinoma cells via regulating miR-185-5p/HOXA13 axis.

作者信息

Sun Y-D, Liu Q, Yang H-X, Tian L, Wang J, Zeng L, Zhou X-W

机构信息

Department of Otolaryngology, Hospital of Traditional Chinese Medicine Affiliated to Southwest Medical University, Luzhou, Sichuan Province, China.

出版信息

Eur Rev Med Pharmacol Sci. 2021 Feb;25(3):1366-1378. doi: 10.26355/eurrev_202102_24845.

Abstract

OBJECTIVE

LncRNA urothelial cancer associated 1 (UCA1) is involved in the development of laryngeal squamous cell carcinoma (LSCC), however, its specific mechanism is not fully clear.

PATIENTS AND METHODS

Quantitative reverse transcription-PCR (RT-qPCR) was conducted to determine the expressions of lncRNA-UCA1, miR-185-5p and homeobox A13 (HOXA13) in LSCC tissues and cell lines. Cell Counting Kit-8 assay, colony formation assay, wound healing assay, Transwell and flow cytometry, DIANA-LncBase V2, as well as Starbase, Targetscan, and Dual-Luciferase reporter gene system were conducted to detect and confirm the crosstalk networks among lncRNA-UCA1, miR-185-5p, and HOXA13.

RESULTS

The levels of UCA1 and HOXA13 were significantly higher and the expression of miR-185-5p was reduced in LSCC tissues and cell lines. Moreover, miR-185-5p was predicted as a target gene for lncRNA UCA1, while HOXA13 was the target gene for miR-185-5p. UCA1 siRNA inhibited the proliferation and invasion of LSCC cells, moreover, the proliferation and invasion of LSCC cells were suppressed by miR-185-5p mimics but were enhanced by miR-185-5p inhibitor. UCA1 siRNA and overexpressed HOXA13 reversed the promotive effects of miR-185-5p inhibitor and inhibitory effects of miR-185-5p mimics on cell proliferation and metastasis, respectively.

CONCLUSIONS

The current findings reveal the important role of lncRNA UCA1/miR-185-5p/HOXA13 regulatory network in LSCC cells, and potentially provide new insights into the pathogenesis of LSCC.

摘要

目的

长链非编码RNA尿路上皮癌相关1(UCA1)参与喉鳞状细胞癌(LSCC)的发生发展,但其具体机制尚不完全清楚。

患者和方法

采用定量逆转录聚合酶链反应(RT-qPCR)检测LSCC组织和细胞系中lncRNA-UCA1、miR-185-5p和同源盒A13(HOXA13)的表达。运用细胞计数试剂盒-8检测、集落形成检测、伤口愈合检测、Transwell检测和流式细胞术,以及DIANA-LncBase V2、Starbase、Targetscan和双荧光素酶报告基因系统来检测和确认lncRNA-UCA1、miR-185-5p和HOXA13之间的相互作用网络。

结果

LSCC组织和细胞系中UCA1和HOXA13水平显著升高,miR-185-5p表达降低。此外,miR-185-5p被预测为lncRNA UCA1的靶基因,而HOXA13是miR-185-5p的靶基因。UCA1小干扰RNA抑制LSCC细胞的增殖和侵袭,此外,miR-185-5p模拟物可抑制LSCC细胞的增殖和侵袭,而miR-185-5p抑制剂则增强其增殖和侵袭。UCA1小干扰RNA和过表达的HOXA13分别逆转了miR-185-5p抑制剂对细胞增殖和转移的促进作用以及miR-185-5p模拟物的抑制作用。

结论

目前的研究结果揭示了lncRNA UCA1/miR-185-5p/HOXA13调控网络在LSCC细胞中的重要作用,并可能为LSCC的发病机制提供新的见解。

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